Recent experimental data indicate that immunity against pre-erythrocytic stages of malaria parasites involves the recognition of the CS protein and several other antigens expressed in sporozoites and/or liver stages of the parasite. The characterization of these antigens and the elucidation of their role in protection, is expected to have a considerable impact on the development of a vaccine designed to prevent sporozoite-induced malaria infection and the development of the pre-erythrocytic stages of these parasites. The present project proposes to characterize the primary structure and identify T and B epitopes present in two conserved antigens expressed in sporozoites, liver and erythrocytic stages of rodent malaria and P. falciparum. One of these antigens is recognized by a CD4+ T cell clone which, upon adoptive transfer to mice, inhibits the development of liver stages of rodent malaria parasites. The other antigen, a plasmodial heat shock protein (hsp-70), appears to be highly conserved among different plasmodial species and has been incriminated in antibody dependent cell mediated cytotoxicity (ADCC) directed against liver stages. We plan to: 1. Characterize the antigen recognized by a protective CD4 + T cell clone. This includes: a) purification and characterization of the physical-chemical properties of the native antigen; b) cloning of the gene encoding the parasite antigen and c) identification of epitopes recognized by protective antibodies, CD4+ and CD8+ T cells. 2. Evaluate the antiplasmodial activity of antibodies and T cells specific for the hsp-70 of P. berghei and of P. falciparum. This includes: a) evaluation of the protective role of anti-hsp antibodies; b) identification of epitopes recognized by CD4+ and CDS+ T cells, generation of epitope-specific T cell clones and assessment of their in vivo anti-plasmodial activity; c) evaluation of sub-unit vaccines containing T and B epitopes of plasmodial hsp-70.